The Dose Makes the Poison

In my house, we’ve recently had a bit of a mouse problem. Or, rather, a mice problem. We’ve known of their presence in the garage for a while. We often let the cats (we have three) out there periodically to roam around, investigate and basically do cat stuff. Well, a few days ago one of the cats left a well-gnawed and barely recognizable mouse-shaped present at the bottom of the steps leading into the garage. That cat earned her keep, I guess, but – ICK!

It gets better. That same day, I walked past one of our other cats, who was lazily sprawled across the kitchen floor. I reached down to pet his head, and there, between his paws was yet another mouse. This one was more intact, but equally dead. More importantly, it was in the kitchen. So, we’re on the lookout for more, and a bit wary. But, like I said, we have three cats – hopefully they’ll quickly address the problem for us.

What’s the chemistry connection? Well, these events brought back a memory of when I was a chemistry grad student. My wife and I were dating back then, and she and her roommate had a similar mouse problem in their apartment. Sadly, however, they had not one cat. What was their solution? First they tried traps – no luck. The little bugger evaded the jaws of death, and still roamed freely through their kitchen cabinets. It kept nibbling its way into boxes of food, and left its tiny mousepoop everywhere in a seemingly unending act of defiance. The stakes were high, and they decided the best strategy would be to poison their cute, yet disgusting, houseguest. Clearly, these two young women were not to be trifled with. (Did I learn a lesson there? You betcha.)

They purchased a couple of d-CON Mouse-Prufe Bait Wedges, and set them in strategic hidden places. (I should point out that back then, live traps were not readily available, so it wasn’t really an option to capture and possibly rehabilitate the mouse) A few days later, the effectiveness of this product became clearly evident as the smell of a dead and rapidly decaying mouse filled the apartment. I seem to remember it took a day or so for the two of them to finally locate the mouse, tucked away behind the bottom drawer of a kitchen cabinet. As neither of them wanted to touch the mouse-corpse, I was called over. I picked up the dead mouse with a newspaper and took it outside to dispose of it. I returned inside where accolades were showered upon me for the manliness of my achievement. Okay, maybe not so much.

The active ingredient that caused the mouse’s demise was warfarin, which works by interfering with normal blood coagulation processes. Basically, the poor critter died from massive internal bleeding. Nice, huh? I try not to think about it.

Sorry, warfarin is not named after Worf, Son of Mogh. But, hey, thank you for playing. photo courtesy CBS Studios Inc

The anticoagulant action, at a reduced level, can have a beneficial effect for people. Warfarin (commonly under the trade name Coumadin) is widely sold as a blood-thinning drug. Warfarin got its name from WARF (Wisconsin Alumni Research Foundation, which funded the initial key research) and the suffix –arin to reflect its coumarin substructure. Sadly, it is not named after Worf, from Star Trek: The Next Generation.

Coumarin is a fragrant heterocyclic organic compound present in several species of plants, such as sweetgrass, sweet clover and woodruff. Coumarin itself has little to no anticoagulant properties. These effects were first noted in the 1920s in cattle that were hemorrhaging after minor procedures such as dehorning or castration (minor procedure?!). It was traced to the cattle having eaten silage containing sweet clover which had become moldy. The fungus combines two relatively harmless coumarin molecules into a dimeric compound, dicoumarol, a powerful anticoagulant.

Warfarin, dicoumarol and other 4-hydroxycoumarins work by inhibiting an enzyme which recycles vitamin K, critical to the function of normal blood coagulation pathways. At low doses this is beneficial for patients at risk for heart attack, stroke or pulmonary embolism due to conditions such as deep vein thrombosis (DVT). It is also given to prevent the formation of blood clots in patients with prosthetic heart valves. Too much warfarin, and, well…you get the picture. As a colleague in safety assessment once said, “The dose makes the poison.” The dosage range from the lowest dose where a compound has the desired effect to the dose where unwanted (adverse) effects begin to outweigh the desired effect is often referred to as the margin or therapeutic window.

Currently, the use of warfarin to kill rodents has been largely replaced by more lethal 4-hydroxycoumarin derivatives, such as brodifacoum (3-[3-(4'-bromobiphenyl-4-yl)-1,2,3,4-tetrahydro-1-naphtyl]-4-hydroxycoumarin). The increased lethality of the newer rodenticides is because, in part, they tend to accumulate in the animal, where warfarin is fairly rapidly excreted. The need for newer, better toxins is also because many populations of rats and mice are now warfarin-resistant. (Evolution at work again!) The downside of the structural modification to offset rapid excretion is that these toxic compounds can then bioaccumulate throughout the food chain, as scavengers and predators feed on the rodents. Not a good thing.

While our mouse problem is an issue and we’re not happy about it, we’re not going to turn to poisons or traps. We’re going to try to reduce the attractiveness of our garage to the mice as much as we can. Failing that, we’ll rely on our cute but ruthless predators. We should probably start sleeping with one eye open.

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One Response to The Dose Makes the Poison

  1. Eli Rabett says:

    Don’t worry, if they are there you will hear them running through the ceiling joists.

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